The search for ideal contrast media for X-ray radiodiagnostic studies has extended over many decades. Bismuth subnitrate was the first radiocontrast agent used for visualization of the alimentary tract. Later, barium sulfate, a safer agent, was introduced. Barium sulfate has remained the most widely used radiographic agent for the alimentary tract (W.H. Strain, International Encyclopedia of Pharmacology and Therapeutics, Section 76, Vol. 1, Radiocontrast Agents, Chapter 1, Historical Development of Radiocontrast Agents, 1971, Pergamon Press). The inorganic, insoluble oral agents like bismuth subnitrate and barium sulfate serve as valuable tools for gastrointestinal radiodiagnosis.
Unlike gastrointestinal radiodiagnosis, urographic and angiographic X-ray procedures, require intravascular administration of a safe, water-soluble, radiopaque contrast medium. Since the introduction of the water-soluble ionic triiodobenzoic acid derivatives, such as diatrizoic acid and iothalamic acid, in the early 1960's, radiographic visualization of the vascular system has become the most important application of X-ray contrast media. These X-ray procedures are valuable in the diagnosis and evaluation of a variety of diseases that involve or cause alterations in normal vascular anatomy or physiology.
In the last ten to fifteen years a major advancement in the area of triiodobenzene X-ray contrast media has been the development of nonionic agents. The main reason for a nonionic radiological composition is to eliminate sensations of pain and warmth caused by the high osmolality associated with the ionic nature of triiodobenzoic acid derivatives. Safer and superior nonionic triiodobenzoic acid derivatives such as iopamidol, iohexol and ioversol have been commercially introduced. Because of their improved chemical structures, which when in solution provide lower osmolality, nonionic agents provide greater patient comfort. Adverse reactions, especially in the sensation of pain, warmth, and hemodynamic effects are greatly reduced when nonionic agents are used.
An ideal intravascular X-ray contrast agent should possess many desirable properties. Some of the most important properties are: 1) maximum X-ray opacity; 2) biological safety; 3) high water solubility; 4) stability; 5) low osmolality; and 6) low viscosity. Therefore, in order to obtain these properties, X-ray contrast agents result in complex molecules.
Iodine is used in triiodobenzene derivative compounds to provide opacification to X-rays. The remaining portion of the molecule provides the means for safe transport of the iodine atoms through the body. The structural makeup of the molecule is critical in providing stability, solubility and other desirable physiochemical properties and biological safety of the contrast agent.
There is a continuing need for agents which substantially meet the desirable properties of an intravascular X-ray contrast agent.